Our objectives are to identify genes or nucleotide sequences of nondefective murine C-type viruses that determine the ability of the viruses to induce leukemias in mice. We also wish to determine the genetic basis for the differences in the type of leukemia induced by different murine retroviruses. Our approach will be to sue genetics and biochemistry. In particular, we will construct site-specific rocombinants between molecularly cloned retroviruses to localize segments of the genome that confer the disease-inducing phenotype. The segments will be further dissected using the same approach, and ultimately, we will determine the nucleotide sequences of the critical regions and then attempt to subject them them to site-specific mutagenesis. These studies shoud provide insight into the role of non-defective C-type viral genomes in bringing about oncogenic transformation.